Except for the FLUAD™ product from Chiron Vaccines, which includes an oil-in-water emulsion adjuvant, influenza vaccines currently in general use are unadjuvanted. These vaccines are described in more detail in chapters 17 & 18 of reference 1. They are based on live virus or inactivated virus, and inactivated vaccines can be based on whole virus, ‘split’ virus or on purified surface antigens (including haemagglutinin and neuraminidase).
More recently, the inclusion of aluminium salt adjuvants has been suggested for influenza vaccines (e.g. see references 2-5). As well as requiring extra mixing steps during manufacture, thereby slowing down overall manufacture, inclusion of these salts is associated with various problems. For example, their insolubility means that adsorbed antigens settle from suspension, so preparation of individual doses from bulk vaccine requires extra care. In addition, binding of antigen to the salts complicates quality control of the final vaccines. In particular, some potency tests for influenza vaccines are based on in vitro immunoassays that require unbound antigen i.e. adsorption to the adjuvant means that these tests cannot be used.
It is an object of the invention to provide further and improved adjuvanted influenza vaccines (for both pandemic and interpandemic use) and methods for their preparation.